Almost all host-invading bacteria have to turn on the expression of their genes required for host invasion including virulence genes at the optimal place and time for maximum effect. These bacteria rely on their sensing mechanisms to detect the presence of host-specific signals, including ionic or pH changes. Our most recent study shows that a group of 47 bacteria share a sensing mechanism, the ExoR-ExoS/ChvI (RSI) invasion switch, which is best understood in Sinorhizobium meliloti. The S. meliloti RSI invasion switch controls the expression of hundreds of bacterial genes involved in invasion and growth in symbiotic plant cells. The host specific signals for the S. meliloti RSI invasion switch, however, remain unknown. Our long-term objective is to understand how S. meliloti and its related pathogenic bacteria sense the presence of a host and create ways to block or alter the sensing mechanism for the benefit of human health. Our current research objective is to identify the host specific signals for the S. meliloti RSI invasion switch. Our recent findings have led us to focus the changes of S. meliloti cells in the infection chamber, where S. meliloti launches their invasion of host cells. This enclosed infection chamber is formed inside a curled root hair but topologically outside the root hair. Our current hypothesis is that plant growth changes ionic concentrations and pH on the root hair surface relative to the surrounding soil due to the pumping of ions in and out of root hairs. The infection chamber is topologically outside the root hair so that ionic concentrations and pH will be similarly changed from those in the soil. This hypothesis is supported by our previously published work on the molecular mechanism of the RSI model and our preliminary results showing that the RSI switch is involved in sensing ionic changes. We propose to 1) determine the ionic changes sensed by the RSI switch, and 2) determine the molecular mechanism governing RSI sensing of ionic changes. The successful completion of the proposed research will show bacterial pathogens can detect unique ionic concentrations on host surface to activate the expression of their virulence genes and provide insights on the bacterial molecular ionic sensing mechanism. Since all living organisms take up and secrete ions, our findings could impact studies of bacterial host sensing mechanisms in general.